The mammalian visual cortex is necessary for vision and has been used over the decades as a model system for the rest of the cerebral cortex. Indeed, research in visual cortex has historically led the way in many fields in neuroscience. In spite of this, little is known about the neural circuits that actually form the visual cortex, how its different types of neurons, located in different layers, actually connect with one another, and whether these connections are specific or not. At the same time, one could argue that to really understand what the cortex does one needs to decipher these circuits in order to provide a framework by which cortical function could be understood as arising from the interactions of its individual cells. Moreover, like in other parts of the mammalian brain, it is likely that each cell type has a particular circuit function, so it could be profitable to study different cortical cell types, searching for their specific functional role. In this application we propose to study a particular type of cortical neuron, the chandelier cell. These cells are GABAergic interneurons which, although they exist in small numbers, could be crucial for the circuit, since they appear to control hundreds of neighboring excitatory cells. Chandelier cells are thought to be circuit switches that could turn off entire cortical columns, although recent work has suggested that, paradoxically, their function could be excitatory and they could serve to trigger intrinsic cortical activity. Due to their paucity, chandeliers have been studied only occasionally. We want to take advantage of a novel genetic method to label them in transgenic mice to carry out a systematic characterization of their structure and function. Using brain slices of mouse visual cortex, we will apply a variety of newly developed optical techniques to visualize and manipulate their activity in order to reveal how they link into cortical circuits, what effect they actually have on excitatory cells and whether or not they serve indeed as circuit switches. These data will clarify the role that chandelier cells play in cortical circuits and help provide a bridge between the cellular and system level understanding of cortical function. The proposed work will lead to a better understanding of the structure and function of neuronal circuits of the visual cortex, and therefore, could potentially have a large impact in the design of novel therapeutic strategies to overcome visual deficits of central origin, such as amblyopia. PUBLIC HEALTH RELEVANCE: We want to understand the function of a type of neuron in the cerebral cortex that could serve as the switch of the circuit. Besides its potential importance for our understanding of how the cortex works, our results could help design strategies to better control, diagnose and repair cortical function.